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Differential Activation of the Unfolded Protein Response in Saccharomyces Cerevisiae During Heterologous Expression of G‐Protein‐Coupled Receptors
Author(s) -
Winget Jason Martin,
VanFossen Amy,
Robinson Clifford,
Robinson Anne Skaja
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a518-b
Subject(s) - g protein coupled receptor , receptor , saccharomyces cerevisiae , biology , microbiology and biotechnology , heterologous expression , receptor expression , adenosine a2a receptor , heterologous , g protein , yeast , biochemistry , gene , adenosine receptor , recombinant dna , agonist
G‐Protein‐Coupled Receptors (GPCRs) are a vital class of integral membrane proteins involved in a wide range of signaling events in the cell. Obtaining adequate amounts of receptor for analysis is a common bottleneck in GPCR research due to low levels of expression in homologous systems. In cases of heterologous expression in which reasonable protein levels are obtained, the receptor is often nonfunctional, requiring a refolding step, often more challenging. We aim to examine the causes of nonfunctional expression in yeast. Previously, we used Saccharomyces cerevisiae to express high levels of functional adenosine A 2A receptor. Expression of a different GPCR, the tachykinin NK 1 receptor, gave high‐level expression, but the protein was retained in nonfunctional form in post‐Golgi vesicles. Here we report the differential activation of the yeast Unfolded Protein Response (UPR) during the inducible expression of these receptors. We find that NK 1 R expression stimulates the UPR, while A 2A expression does not. We are currently investigating how this differential response impacts receptor localization. Support provided by NIH to C.R.R and A.S.R. and NSF to J.M.W.